All literature and patent citations appearing in this specification are hereby incorporated herein by reference.
First transition series elements are essential to the replication and growth of all cells and viruses. They are essential co-enzymes required in a variety of metabolic processes. Iron and copper can catalyze free radical formation leading to oxidative damage to tissues. Consequently, alterations of the bioavailability and function of first transition series elements can affect cell systems, metabolic processes, and complex phenomena that are affected by such processes.
It is generally appreciated that most body odors arise from chemical byproducts of microbial growth. Thus, antimicrobial agents such as triclosan are commonly added to personal care products and cosmetics to inhibit development of body odors (such as underarm odor) through inhibition of microbial growth. See, Antiperspirants and Deodorants, 2d Ed., K. Laden, Ed., 1999, Marcel Dekker, Inc., New York, N.Y.
It is also generally appreciated that tooth decay, gingival inflammation and periodontal disease are initiated by microbial growth on surfaces in the oral cavity. Thus, antimicrobial agents such as triclosan have been incorporated into toothpastes to inhibit such processes. See, Oral Hygiene Products and Practice, 1988 Morton Prader, Ed., Marcel Dekker, Inc., New York, N.Y.
It is also generally appreciated that skin aging is, in part, a consequence of cumulative oxidative damage to the skin, particularly related to free radical generation consequent to exposure to solar ultraviolet radiation. In part, such free radical generation occurs through iron-catalyzed Fenton reactions. Thus, personal care/cosmetics preparations have been formulated containing reducing agents such as vitamin E and C to scavenge free radicals and other oxidizing species and it has been proposed that iron chelators be added to sunscreens to inhibit free radical generation. See, Sunscreens Development Evaluation and Regulatory Aspects, 1997, N. J. Lowe, N. A. Shaath, M. A. Pothak, Eds., Marcel Dekker, Inc., New York, N.Y.
It is also generally appreciated that first transition series elements act as coenzymes in a variety of enzymatic systems (metalloenzymes). Interference with access to the metal site by agents that chelate, or combine with, the metal at open coordination sites results in inhibition of the enzymatic activity of such enzymes. See, Inhibition of Matrix Metalloproteinases Therapeutic Applications, 1999 R. A. Greenwald, S. Zucker, L. M. Golub, Eds., New York Academy of Sciences ANYAA9878 1-761.
It is also generally appreciated that complex tissue processes may be affected by one or more processes in which first transition series elements play a role. For example, reperfusion injury may be related to hydroxyl free radicals arising from iron-catalyzed Fenton reactions (see, "Prevention of Hydroxyl Radical Formation: A Critical Concept for Improving Cardioplegia. Protective Effects of Deferoxamine," P. Menasche, et al., Circulation, 1987, vol. 76 (Suppl. V), 180-185) and local release of matrix metalloproteinase enzymes (see, "Inhibition of Matrix Metalloproteinase-2 (MMP-2) Released During Reperfusion Following Ischemia Reduces Myocardial Stunning Injury," G. Sawicki, et al., Can J. Cardiol. Vol. 15, Suppl. D, 1999).
Published international patent application WO 97/01360 ("Compounds With Chelation Affinity and Selectivity For First Transition Series Elements, and Their Use in Medical Therapy and Diagnosis," applicant: CONCAT, LTD., publication date Jan. 16, 1997, application number: PCT/US96/10785) discloses compositions and methods relating to a family of chelating agents having high affinity and specificity for first transition series elements. claims include their use in inhibiting bacterial and fungal growth on a surface, including body surfaces, treating conditions dependent on bioavailability of first transition series elements in a patient, and treating conditions that are mediated by free radical or oxidation related tissue destruction.
The present specification demonstrates that the family of chelating agents disclosed in WO 97/01360 are capable of being used in cosmetics and personal care products to inhibit odor development (such as for example underarm odor), to inhibit replication of microorganisms associated with tooth decay and oral disease, and to inhibit oxidation and free radical damage to the skin. This specification also demonstrates that this family of chelating agents is capable of inhibiting enzymatic activity of metalloenzymes containing first transition series elements. Still further, this specification demonstrates that this family of chelating agents inhibits reperfusion injury, possibly as a consequence of their ability to inhibit generation of hydroxyl free radicals and/or inhibition of metalloenzymes such as the matrix metalloproteinases.
This invention resides in the discovery that a class of substituted polyaza compounds showing affinity and selectivity for first transition series elements (atomic numbers 21-30), by virtue of their ability to decrease the bioavailability and/or biochemical action of the first transition series elements, are useful in personal care products to decrease odor arising from microbial growth on body surfaces and in body cavities, decrease microbial growth on teeth, plaque, and gums that cause tooth decay and gum disease, inhibit oxidative damage to the skin, inhibit enzymatic action of metalloenzyme dependent on first transition series elements, and inhibit reperfusion injury. These effects are achieved by application or administration of the substituted polyaza compounds as either free ligands or as conjugated compounds, or as physiological salts of the free ligands or conjugated compounds.